US11981660B2ActiveUtilityA1
Neurite outgrowth promoters and uses thereof
Est. expiryMar 21, 2038(~11.7 yrs left)· nominal 20-yr term from priority
C07D 403/06A61P 25/30A61P 25/18C07D 233/84
45
PatentIndex Score
0
Cited by
17
References
19
Claims
Abstract
Provided herein are compounds useful in treating a central nervous system disorder associated with neuronal and/or axonal damage, methods for their preparation, and related pharmaceutical compositions. For example provided herein are compounds of Formula (I): and pharmaceutically acceptable salts and compositions including the same.
Claims
exact text as granted — not AI-modifiedWhat is claimed:
1. A compound of Formula (I), or a pharmaceutically acceptable salt thereof:
wherein:
m is 3, 4, or 5;
n is 1 or 2;
HET is C 3-7 heterocycloalkyl;
each X independently is S or O;
R 1 is unsubstituted C 1-6 alkyl, C 0-3 alkylene-C 3-7 cycloalkyl, C 0-3 alkylene-C 3-7 heterocycloalkyl, phenyl, or C 0-3 alkylene-C 2-6 heteroaryl;
R 2 is unsubstituted C 1-6 alkyl, C 1-3 alkylene-C 3-7 cycloalkyl, C 1-3 alkylene-C 3-7 heterocycloalkyl, or C 1-3 alkylene-C 2-6 heteroaryl; and
R 3 is C 1-8 alkyl, C 0-3 alkylene-C 3-7 cycloalkyl, C 0-3 alkylene-C 3-7 heterocycloalkyl, C 0-3 alkylene-C 6-10 aryl, or C 0-3 alkylene-C 2-6 heteroaryl; and
each heterocycloalkyl and heteroaryl group independently has 1, 2, or 3 ring heteroatoms selected from N, O, and S.
2. The compound or salt of claim 1 , wherein m is 4.
3. The compound or salt of claim 1 , wherein n is 1.
4. The compound or salt of claim 3 , wherein X is S.
5. The compound or salt of claim 1 , wherein HET comprises dihydroimidazolyl, piperazinyl, diketopiperazinyl, C 2-5 cyclic guanidinyl, C 2-5 cyclic ureayl, C 2-5 cyclic thioureayl, aziridinyl, oxiranyl, thiiranyl, azirinyl, oxirenyl, thiirenyl, azetidinyl, oxetanyl, thetanyl, azetenyl, oxetenyl, thetenyl, pyrrolidinyl, tetrahydrofuranyl, tetrahydrothiophenyl, piperidinyl, tetrahydropyranyl, tetrahydrothiopyranyl, pyranyl, thiopyranyl, or morpholinyl.
6. The compound or salt of claim 5 , wherein HET is
7. The compound or salt of claim 1 , wherein R 1 is C 1-6 alkyl or phenyl.
8. The compound or salt of claim 7 , wherein C 1-6 alkyl is methyl, ethyl, propyl, isopropyl, butyl, 2-butyl, or isobutyl.
9. The compound of claim 1 , wherein R 1 is:
(i) methyl or isobutyl; or
(ii) CH 2 -cyclohexyl, or
(iii) phenyl, or
(iv) 3-methylpyridinyl.
10. The compound or salt of claim 1 , wherein R 2 is:
11. The compound or salt of claim 1 , wherein R 3 is C 1-8 alkyl, C 0-3 alkylene-C 3-7 cycloalkyl, C 1-3 alkylene-C 6-10 aryl, or C 1-3 alkylene-C 2-6 heteroaryl.
12. The compound or salt of claim 11 , wherein R 3 is:
(i) s-butyl; or
13. The compound or salt of claim 1 , wherein:
m is 4;
n is 1;
X is S;
HET is
R 1 is C 1-6 alkyl or phenyl;
R 2 is C 1-3 alkylene-C 3-7 cycloalkyl, and
R 3 is C 1-8 alkyl, C 0-3 alkylene-C 3-7 cycloalkyl, or C 1-3 alkylene-C 6-10 aryl.
14. The compound or salt of claim 1 , wherein R 2 is ethyl.
15. A compound or pharmaceutically acceptable salt thereof having a structure as listed in Table A:
TABLE A
Compound #
R 1
R 2
R 3
A1
methyl
4-methylpentyl
s-butyl
A2
methyl
4-methylpentyl
cyclopentyl
A3
methyl
4-methylpentyl
(CH 2 ) 3 —Ph
A4
methyl
CH 2 CH 2 -cyclohexyl
s-butyl
A5
methyl
CH 2 CH 2 -cyclohexyl
cyclopentyl
A6
methyl
CH 2 CH 2 -cyclohexyl
(CH 2 ) 3 —Ph
A7
methyl
CH 2 -4-methylcyclohexyl
s-butyl
A8
methyl
CH 2 -4-methylcyclohexyl
cyclopentyl
A9
methyl
CH 2 -4-methylcyclohexyl
(CH 2 ) 3 —Ph
A10
isobutyl
4-methylpentyl
s-butyl
A11
isobutyl
4-methylpentyl
cyclopentyl
A12
isobutyl
4-methylpentyl
(CH 2 ) 3 —Ph
A13
isobutyl
CH 2 CH 2 -cyclohexyl
s-butyl
A14
isobutyl
CH 2 CH 2 -cyclohexyl
cyclopentyl
A15
isobutyl
CH 2 CH 2 -cyclohexyl
(CH 2 ) 3 —Ph
A16
isobutyl
CH 2 -4-methylcyclohexyl
s-butyl
A17
isobutyl
CH 2 -4-methylcyclohexyl
cyclopentyl
A18
isobutyl
CH 2 -4-methylcyclohexyl
(CH 2 ) 3 —Ph
A19
phenyl
4-methylpentyl
s-butyl
A20
phenyl
4-methylpentyl
cyclopentyl
A21
phenyl
4-methylpentyl
(CH 2 ) 3 —Ph
A22
phenyl
CH 2 CH 2 -cyclohexyl
s-butyl
A23
phenyl
CH 2 CH 2 -cyclohexyl
cyclopentyl
A24
phenyl
CH 2 CH 2 -cyclohexyl
(CH 2 ) 3 —Ph
A25
phenyl
CH 2 -4-methylcyclohexyl
s-butyll
A26
phenyl
CH 2 -4-methylcyclohexyl
cyclopentyl
A27
phenyl
CH 2 -4-methylcyclohexyl
(CH 2 ) 3 —Ph.
16. The compound or salt of claim 15 , selected from the group consisting of
17. A pharmaceutical composition comprising the compound or salt of claim 1 and a pharmaceutically acceptable carrier.
18. A method of treating a central nervous system (CNS) disorder or a peripheral nervous system (PNS) disorder associated with neuronal and/or axonal damage in a subject in need thereof, comprising administering to the subject the compound or salt of claim 1 , in an amount effective to repair neuronal and/or axonal damage and treat the CNS disorder or the PNS disorder.
19. A method of treating nerve degeneration in a subject undergoing cancer therapy, comprising administering to the subject the compound or salt of claim 1 , in an amount effective to treat the nerve degeneration.Cited by (0)
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